速尿处理的断奶大鼠的补盐、生长与肾钙质沉着症

Gratny L L, Ringer K, Hall R T, Alon U S

Division of Neonatology, Children's Mercy Hospital, University of Missouri-Kansas City, USA.

Biol Neonate. 1997;71(1):37-45. doi: 10.1159/000244395.

OBJECTIVE

Furosemide treatment in the human neonate is associated with sodium depletion, growth retardation, hypercalciuria and nephrocalcinosis. Dietary sodium intake is known to directly influence urinary calcium excretion. The objectives of this study were to create a rat model of furosemide-induced nephrocalcinosis and to test the effects of dietary sodium supplementation on growth, electrolyte balance, calciuria, and renal calcifications.

METHODS

Initially, 18 weanling Sprague-Dawley rats were randomly divided into three groups. Groups A (control) and B were fed a basal diet. Group C was fed a sodium-enriched diet. Groups B and C received furosemide (40 mg/kg) intraperitoneally daily for 28 days. At the end of the study, serum, urine, and kidney samples were obtained for biochemical and histologic analyses. The three groups were then compared for differences in growth, electrolyte homeostasis, calcium excretion and nephrocalcinosis. Subsequently an additional 15 rats were studied to confirm our findings regarding urinary calcium excretion and kidney calcifications.

RESULTS

Treatment with furosemide without sodium supplementation (group B) resulted in decreased weight gain compared with group A (137.5 +/- 12.9 vs 154.0 +/- 10.6 g; p < 0.05), hypokalemia (3.7 +/- 0.1 vs. 4.4 +/- 0.4 mEq/l; p < 0.05), and nephrocalcinosis (187.1 +/- 155 vs. 18.8 +/- 6.9 micrograms Ca/g dry kidney; p < 0.05). Sodium supplementation (group C) normalized weight gain and corrected electrolyte abnormalities without increasing calciuria or nephrocalcinosis.

CONCLUSIONS

We conclude that in this animal model, chronic furosemide treatment results in growth failure and development of nephrocalcinosis. Sodium supplementation protects against the deleterious effects of furosemide on weight gain and electrolyte homeostasis with no adverse effect on nephrocalcinosis.

目的

人类新生儿使用速尿治疗与钠耗竭、生长发育迟缓、高钙尿症和肾钙质沉着症有关。已知饮食中的钠摄入量会直接影响尿钙排泄。本研究的目的是建立速尿诱导的肾钙质沉着症大鼠模型，并测试补充饮食钠对生长、电解质平衡、钙尿症和肾钙化的影响。

方法

最初，将18只断乳的Sprague-Dawley大鼠随机分为三组。A组（对照组）和B组喂食基础饮食。C组喂食高钠饮食。B组和C组每天腹腔注射速尿（40mg/kg），持续28天。在研究结束时，获取血清、尿液和肾脏样本进行生化和组织学分析。然后比较三组在生长、电解质稳态、钙排泄和肾钙质沉着症方面的差异。随后又对另外15只大鼠进行研究，以证实我们关于尿钙排泄和肾钙化的发现。

结果

未补充钠的速尿治疗组（B组）与A组相比，体重增加减少（137.5±12.9 vs 154.0±10.6g；p<0.05），出现低钾血症（3.7±0.1 vs. 4.4±0.4mEq/l；p<0.05）和肾钙质沉着症（187.1±155 vs. 18.8±6.9微克钙/克干肾；p<0.05）。补充钠（C组）使体重增加恢复正常，并纠正了电解质异常，而不会增加钙尿症或肾钙质沉着症。